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Published ahead of print 1 May 2013, doi: 10.1128/JVI.00373-13 JVI.00373-13
Genetic requirement for hemagglutinin glycosylation and its implications for the influenza A H1N1 evolution
Jin Il Kima,b,
Ilseob Leea,b,
Sehee Parka,b,
Min-Woong Hwanga,b,
Joon-Yong Baea,b,
Sangmoo Leea,b,
Jun Heoa,b,
Mee Sook Parka,b,
Adolfo Garc?a-Sastrec,d,e and
Man-Seong Parka,b#
+ Author Affiliations
aDepartment of Microbiology
bCenter for Medical Science Research, College of Medicine, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea
cDepartment of Microbiology
dDepartment of Medicine, Division of Infectious Diseases
eGlobal Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USA
ABSTRACT
Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLG-free HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus. Hence it is possible that descendants of the 2009 H1N1 virus might recapitulate the acquisition of HA head glycoslylation sites through their evolutionary drift as a means to evade pre-existing immunity. Here we evaluate the evolution signature of glycosylations found in the globular head region of H1 HA in order to determine their impact in virulence and transmission of H1N1 viruses. We identified a polymorphism at HA residue 147 associated with the acquisition of glycosylation at residues 144 and 172. By in vitro and in vivo analyses using mutant viruses, we also found that the polymorphism at HA residue 147 compensated for the loss of replication, virulence and transmissibility associated with the presence of the N-linked glycans. Our findings suggest that the polymorphism in H1 HA at position 147 modulate viral fitness by buffering the constraints caused by N-linked glycans, and provide insights into the evolution dynamics of influenza viruses with implications in vaccine immunogenicity.
Genetic requirement for hemagglutinin glycosylation and its implications for the influenza A H1N1 evolution
Jin Il Kima,b,
Ilseob Leea,b,
Sehee Parka,b,
Min-Woong Hwanga,b,
Joon-Yong Baea,b,
Sangmoo Leea,b,
Jun Heoa,b,
Mee Sook Parka,b,
Adolfo Garc?a-Sastrec,d,e and
Man-Seong Parka,b#
+ Author Affiliations
aDepartment of Microbiology
bCenter for Medical Science Research, College of Medicine, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea
cDepartment of Microbiology
dDepartment of Medicine, Division of Infectious Diseases
eGlobal Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, New York 10029, USA
ABSTRACT
Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLG-free HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus. Hence it is possible that descendants of the 2009 H1N1 virus might recapitulate the acquisition of HA head glycoslylation sites through their evolutionary drift as a means to evade pre-existing immunity. Here we evaluate the evolution signature of glycosylations found in the globular head region of H1 HA in order to determine their impact in virulence and transmission of H1N1 viruses. We identified a polymorphism at HA residue 147 associated with the acquisition of glycosylation at residues 144 and 172. By in vitro and in vivo analyses using mutant viruses, we also found that the polymorphism at HA residue 147 compensated for the loss of replication, virulence and transmissibility associated with the presence of the N-linked glycans. Our findings suggest that the polymorphism in H1 HA at position 147 modulate viral fitness by buffering the constraints caused by N-linked glycans, and provide insights into the evolution dynamics of influenza viruses with implications in vaccine immunogenicity.
